Confirmed virologic failure is defined as confirmed plasma HIV-1 RNA levels > 1000 copies/mL at or after week 16 and before week 24, or confirmed HIV-1 RNA levels> 200 copies/mL at or after week 24. Participants who discontinued the study with an unconfirmed virologic failure (HIV-1 RNA > 1000 copies at 16 weeks or HIV-1 RNA level > 200 copies/mL at or after week 24) are considered as virologic failures at the study visit week of the unconfirmed value. Time to virologic failure is defined as the time from study entry to the planned visit week of the initial failure.

Product-limit estimates for the survival function were used to estimate the cumulative probability of virologic failure over time and its corresponding 95% confidence interval for each treatment group.

Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet.

Other Names:

Prezista

TMC-114

DRV

Drug: Ritonavir

Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food.

Other Names:

Norvir

RTV

Drug: Tenofovir disoproxil fumarate

Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day.

Other Names:

Viread

TDF

Drug: Emtricitabine

Emtricitabine was administered orally once a day as one 200 mg capsule.

Other Names:

Emtriva

FTC

Coviracil

Drug: Placebo for Maraviroc

Placebo for maraviroc was administered orally once a day as one tablet.

Detailed Description:

There are now several HIV treatment options for a person with HIV infection who has not yet been treated. Most people who receive treatment and take their medications as directed have a good result. This is usually determined by measuring the amount of HIV in the blood (viral load). The best response is when HIV cannot be found (less than 50 copies/mL) in the blood. However, it has recently become clear that some people with HIV who are receiving effective HIV drugs continue to have more health problems than people without HIV infection. Sometimes, there is damage to organs in the body, including bone, kidneys, and the brain.

Eligibility

Ages Eligible for Study:

18 Years and older (Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

HIV-1 infection

No evidence of exclusionary resistance mutations defined as evidence of any major NRTI mutation according to the current IAS list of HIV-1 Resistance Mutations Associated with Drug Resistance, or any DRV RAMs (refer to the A5303 PSWP for a list of these mutations) on any genotype; or evidence of significant NRTI or DRV resistance on any phenotype performed at any time prior to study entry. NNRTI-associated resistance mutations were not exclusionary.

ARV drug-naïve, defined as </=10 days of ART at any time prior to study entry, except in the instances defined in section 4.1.3 of the protocol.

R5-only tropism based on Trofile testing performed within 90 days prior to study entry.

Screening HIV-1 RNA >1000 copies/mL obtained within 90 days prior to study entry by any FDA-approved test for quantifying HIV-1 RNA at any laboratory that has a CLIA certification or its equivalent.

Known hepatitis C virus (HCV) antibody status (performed at any laboratory that had a CLIA certification or its equivalent).

Certain laboratory values obtained within 60 days prior to study entry, as defined in section 4.1.7 of the protocol.

For women of reproductive potential, negative serum or urine pregnancy test with a sensitivity of ≤25 mIU/mL within 72 hours prior to study entry.

Female subjects of reproductive potential, who were participating in sexual activity that could lead to pregnancy, must agree to use at least one reliable method of contraception (as defined in section 4.1.9.1 of the protocol) while receiving the study drugs and for 6 weeks after stopping the medications.

Female subjects who were not of reproductive potential or whose male partner(s) had azoospermia were eligible to take study drugs without the use of contraceptives.

Ability and willingness of subject or legal guardian/representative to give written informed consent.

Willingness to undergo neuropsychological testing.

DXA scan performed after confirmation of the subject's eligibility by Trofile testing but no more than 4 weeks prior to randomization.

New use of hormonal therapies within 6 months prior to study entry. (Stable therapy for ≥6 months was permitted.)

New use of oral contraceptive pills (OCPs) in the past 3 months. (Stable therapy for ≥3 months was permitted.)

Any oral, intravenous, or inhaled steroids within 30 days prior to study entry. (Intranasal steroids and topical corticosteroids were allowed.)

Known allergy/sensitivity to study drugs or their formulations. (A history of sulfa allergy was not an exclusionary condition.)

Known hypersensitivity to soy lecithin.

Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or was clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry. (Oral candidiasis, vaginal candidiasis, mucocutaneous herpes simplex, and other minor illnesses (as judged by the site investigator) were not exclusionary conditions.)

Requirement for any current medications that were prohibited with any study drugs. (Prohibited medications must be discontinued at least 30 days prior to entry. Refer to the A5303 PSWP for a list of prohibited medications.)

Current or prior use of biphosphonates, teriparatide, raloxifene, or denosumab.

Weight >300 lbs (exceeds weight limit of DXA scanners).

History after 18 years of age of fracture of the spine, hip, wrist, or other site thought to be related to osteoporosis or bone fragility.

Currently breastfeeding.

Any active psychiatric illness including schizophrenia, severe depression, or severe bipolar affective disorder that, in the opinion of the investigator, could confound the analysis of the neurological examination or neuropsychological test results.

Active drug or alcohol abuse that, in the investigator's opinion, could prevent compliance with study procedures or confound the analysis of study endpoints.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01400412